The discoveries made by researchers could lead to improved methods for managing high blood pressure.
Researchers from the University of Virginia School of Medicine have uncovered how certain cells possess the remarkable ability to change their roles in assisting our bodies in regulating blood pressure.
These cells include smooth muscle cells that line our blood vessels. Under normal circumstances, these cells help manage blood pressure by contracting and relaxing. However, when blood pressure drops significantly and remains low for extended periods, certain smooth muscle cells in the kidneys, along with other kidney cell types, can adopt a new function: producing renin. Renin is a substance usually created by specialized kidney cells to help stabilize blood pressure.
Researchers have been unclear about the genetic triggers that initiate this rapid shift to renin production. However, the UVA team has uncovered some answers, pinpointing a vital biological “switch” that governs this transformation, shedding light on the cells’ unique capabilities.
“Understanding how this switch operates will deepen our knowledge of how our bodies regulate blood pressure,” explained researcher R. Ariel Gomez, MD, from UVA’s Child Health Research Center. “Recognizing how vascular cells can alter their identity may assist in developing new treatments for high blood pressure and related vascular disorders.”
Insights into Blood Pressure
Gomez, along with collaborator Maria Luisa S. Sequeira-Lopez, MD, is spearheading research on the role of renin in blood pressure regulation. In their latest study, they collaborated with UVA senior scientist Jason P. Smith, PhD, and others to further investigate how certain cells can recollect how to produce renin long after ceasing to do so.
The UVA researchers identified numerous biological mechanisms involved in this process. They found nine specific genes that are crucial in regulating the three biological “pathways” related to renin production. These genes are responsible for stopping smooth muscle cells from creating renin and for signaling them to start again when necessary. The scientists noted that while these cells naturally cease renin production, they remain in a state that allows them to respond quickly when needed.
Additionally, the researchers discovered elements that activate the genes to restart renin production. This “epigenetic” switch is essential for comprehending how renin production is regulated in cells that do not typically manufacture renin.
“We anticipated that the segment of the genome where this gene is found would be inaccessible when renin is off. Surprisingly, this area remains generally accessible in cells that are prepared to go back to producing renin when required,” stated Smith. “Ultimately, since renin is vital for our health, gaining a deeper understanding of how our bodies control its production could serve as a foundation for treating hypertension and assessing the long-term impacts of common blood pressure medications on kidney health and disease.”
The research conducted by the UVA team offers a detailed framework for understanding renin regulation, as noted in their recent scientific publication. Their findings provide crucial guidance for future studies and may yield important insights into the development of kidney damage known as fibrosis. The researchers suggest that focusing on the processes that control renin could pave the way for new treatments for high blood pressure and cardiovascular issues.
“Our goal now is to find markers and potential targets to reduce and ideally control the negative effects associated with chronic stimulation of renin-producing cells,” said Sequeira-Lopez. “It is essential to grasp the fundamental mechanisms of our cells to devise more effective therapies that have fewer or no side effects.”
This research received support from the National Institutes of Health through grants P50DK096373, R01DK116718, and R01HL148044.
